IMMUNOTHERAPY EFFICIENCY IN RHINOSINUSITIS PATIENTS

Latent rhinosinusitis proceeds without facial pain symptoms. Immune deficiency plays a leading role in pathogenesis of the disease latency. Substance P seems to be a universal mediator of painful irritation and inflammation. The objective of our study was to determine effectiveness of therapies in patients with latent rhinosinusitis, in terms of substance P levels.

We treated 148 patients with rhinosinusitis, being free of local pains. All the patients underwent clinical and laboratory examination, including immune profile assessment, measurements of serum cytokines IL-1β, IL-4, IL-6, IL-8, IL-10, TNFα, IFNγ, and substance P. To correct a secondary immunodeficiency, the standard treatment of rhinosinusitis in a subgroup of the patients was accomplished by immunomodulatory drugs from the first day of therapy. The latter drugs were avoided for the rest of study group. Efficacy of treatment was evaluated by clinical signs and laboratory parameters on day 7 of the medication.

 Pre-treatment levels of substance P were determined in all the patients with latent clinical course and lack of pain symptoms. Low substance P levels (< 100 pg /ml) were considered as indications for immunomodulatory therapy, due to immune deficiency confirmed by the cytokine imbalance. Choice of a specific drug was dependent on immunopathogenesis, i.e., for catarrhal rhinosinusitis and deficiency of cellular immunity, we administered IFN-ES-lipint; in cases of purulent rhinosinusitis, Likopid was applied. The patients treated with immunomodulatory drugs showed improvement of immune indexes by the 7th day of treatment, along with return of substance P levels to control values typical to healthy persons. Among patients with low substance P levels and immune deficiency (without immunomodulatory treatment), the immune parameters and substance P levels did not exhibit any sufficient changes over time.

Low contents of substance P (SP ≤ 100 pg /ml) in blood serum in pain-free patients with latent rhinosinusitis are indicative of immune deficiency and may serve as an indication for immune modulation therapy. Individual selection of the pathogenetically proven schedule therapy, when treating patients with latent (painless) rhinosinusitis may result into effective prevention of severe inflammation, normalization of immune response, prevention of a protracted disease course, and appropriate complications, as well as shortening of treatment terms to 8-10 days

1. Абдулкеримов Х.Т., Гаращенко Т.И., Кошель В.И., Свистушкин В.М., под ред. Рязанцева С.В. Принципы этиопатогенетической терапии острых синуситов: методические рекомендации. СПб.: Полиформ Групп, 2014. 40 с. [Abdulkerimov Kh.T., Garashchenko T.I., Koshel’ V.I., Svistushkin V.M., Ryazantsev S.V., red. Principles etiopathogenic therapy of acute sinusitis: guidelines]. St. Petersburg: Poliform Grupp, 2014. 40 p.

2. Адашинская Г.А., Мейзеров Е.Е. Многомерный вербально-цветовой тест // Боль, 2005. №1 (6). С. 26-33. [Adashinskaya G.A., Meyzerov E.E. Multivariate verbal-color test. Bol’ = Pain, 2005, no. 1 (6), pp. 26-33. (In Russ.)]

3. Азнабаева Л.Ф., Шарипова Э.Р., Арефьева Н.А., Симбирцев А.С., Викторова Т.В., Зайнуллина А.Г. Патогенетические особенности течения гнойного воспаления верхних дыхательных путей (риносинусита) в зависимости от генетического контроля продукции интерлейкина 1β // Цитокины и воспаление, 2011. № 2. С. 50-55. [Aznabaeva L.F., Sharipova E.R., Aref ’eva N.A., Simbirtsev A.S., Viktorova T.V., Zaynullina A.G. Pathogenetic features of the upper respiratory tract purulent inflammation (rhinosinusitis), depending on the genetic control of interleukin 1β production. Tsitokiny i vospalenie = Cytokines and Inflammation 2011, Vol. 10, no. 2, pp. 50-55. (In Russ.)]

4. Андронова Т.М., Пинегин Б.В., Козлов И.Г. Ликопид (ГМПД) – современные представления. 5-е изд., доп. и перераб. Россия, 2009. 20 с. [Andronova T.M., Pinegin B.V., Kozlov I.G. Likopid (GMPD) – modern representations. 5th ed., ext. and rev.]. Russia, 2009. 20 p.

5. Бойко Н.В., Колесников В.Н., Левченко Е.В. Статистика причин затруднения носового дыхания // Российская ринология, 2007. № 2. С. 24-25. [Boyko N.V., Kolesnikov V.N., Levchenko E.V. Statistics reasons nasal breathing difficulties. Rossiyskaya rinologiya = Russian Rhinology, 2007, no. 2, pp. 24-25. (In Russ.)]

6. Бойко Н.В., Стагниева И.В. Дифференциальная диагностика лицевых болей // Российская ринология, 2012. № 4. С. 39-41. [Boyko N.V., Stagnieva I.V. Differential diagnosis of facial pain. Rossiyskaya rinologiya = Russian Rhinology, 2012, Vol. 20, no. 4, pp. 39-41. (In Russ.)]

7. Волков А.Г., Стагниева И.В Острый и хронический фронтит: современный взгляд проблему // Вестник оториноларингологии, 2012. № 6. С. 98-102. [Volkov A.G., Stagnieva I.V. Acute and chronic sinusitis: the current view of the problem. Vestnik otorinolaringologii = Bulletin of Otorhinolaryngology, 2012, no. 6, pp. 98-102. (In Russ.)]

8. Волков А.Г., Стагниева И.В., Ерошенко А.Ю. Значимость локального болевого симптома при фронтите // Вестник оториноларингологии, 2010. № 4. С.38-40. [Volkov A.G., Stagnieva I.V., Eroshenko A.Yu. Significance of local pain syndrome in patients with frontitis. Vestnik otorinolaringologii = Bulletin of Otorhinolaryngology, 2010, no. 4, pp. 38-40. (In Russ.)]

9. Гурьянова С.В., Козлов И.Г., Мещерякова Е.А., Алексеева Л Г., АндроноваТ. М. Глюкозаминилмурамилдипептид нормализует баланс Th1/Th2 при атопической бронхиальной астме // Иммунология, 2009. Т. 30, № 5. С. 305309. [Guryanova S.V., Kozlov I.G., Meshcheryakova E.A., Alekseeva L.G., Andronova T.M. Investigation into the influence of glucosaminylmuramyl dipeptide on the normalization of Тh1/Th2 balance in patients with atopic bronchial asthma. Immunologia = Immunology, 2009, Vol. 30, no. 5, pp. 305-309. (In Russ.)]

10. Кетлинский С.А., Симбирцев А.С. Цитокины. СПб.: Фолиант, 2008. 552 с. [Ketlinskiy S.A., Simbirtsev A.S. Cytokines]. St. Petersburg: Foliant, 2008. 552 p.

11. Стагниева И.В., Гукасян Е.В. Оценка болевого симптома при заболеваниях носа и околоносовых пазух // Медицинский вестник Юга России, 2012. № 2. С. 70-73. [Stagnieva I.V., Gukasyan E.L. Facial pain in diseases of nose and paranasal sinuses. Meditsinskiy vestnik Yuga Rossii = Medical Bulletin of the South of Russia, 2012, no. 2, pp. 70-73. (In Russ.)]

12. Стагниева И.В., Бойко Н.В. Головная и лицевая боль при риносинусите // Медицинский вестник Юга России, 2014, № 3. С. 55-59. [Stagnieva I.V., Boyko N.V. Headache and facial pain in rhinosinusitis. Meditsinskiy vestnik Yuga Rossii = Medical Bulletin of the South of Russia, 2014, no. 3, pp. 55-59. (In Russ.)]

13. Усова С.В., Бажутин Н.Б., Войтенко А.В., Таргонский С.Н. Получение липосомального препарата рекомбинантного альфа-2b интерферона «РЕАФЕРОН-ЕС-ЛИПИНТ» и опыт применения его для экстренной профилактики гриппа и других острых респираторных вирусных инфекций // Поликлиника, 2009. № 1. С. 110-112. [Usova S.V., Bazhutin N.B., Voytenko A.V., Targonskiy S.N. Obtaining liposomal formulation of recombinant interferon alfa-2b «REAFERON-ESLIPINT» and experience of its application for emergency prevention of influenza and other acute respiratory viral infections. Poliklinika = Polyclinic, 2009, no. 1, pp. 110-112. (In Russ.)]

14. Янов Ю.К. Современные возможности оптимизации медикаментозной терапии острых синуситов // Российская оториноларингология, 2004. № 4. С. 10-15. [Yanov Yu.K. Modern possibilities of optimizing drug therapy of acute sinusitis. Rossiyskaya otorinolaringologiya = Russian Otorhinolaryngology, 2004, no. 4, pp. 10-15. (In Russ.)]

15. Koon H.W., Pothoulakis C. Immunomodulatory properties of substance P: the gastrointestinal system as a model. Ann. N.Y. Acad. Sci., 2006, Vol. 1088, pp. 23-40.

16. Marriott I., Bost K.L. Substance P receptor mediated macrophage responses. Adv. Exp. Med. Biol., 2001, no. 493, pp. 247-254.

17. Omoigui S. The biochemical origin of pain – Proposing a new law of pain: The origin of all pain is inflammation and the inflammatory response. Part 2 of 3 – A unifying law of pain. Medical Hypotheses, 2007, Vol. 69, Is. 6, pp. 1169-1178.

18. Ren K., Dubner R. Interactions between the immune and nervous systems in pain. Nat. Med., 2010, Vol. 16, no. 11, pp. 1267-1276.